Squamous Cell Carcinoma, Head And NeckPhase 2NCT02649530
A Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing WNT974 in people with Squamous Cell Carcinoma, Head And Neck, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
Given that up-regulation of the Wnt pathway has been identified as having a significant role in carcinogenesis in advanced head and neck squamous cell carcinoma, the investigator believes that inhibition of Porcupine via WNT974 will result in tumor control hence improvement in disease free and overall survival in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma, Head And Neck
- What is being tested?
- WNT974
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento Jul 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically documented diagnosis of locally advanced or metastatic SCC (Squamous Cell Carcinoma) of the head and neck no longer amenable to curative surgical resection or radiation therapy.
- Refractory to platinum-based therapy (defined as disease progression within 6 months of last dose of platinum chemotherapy)
- Patient is able swallow and absorb oral medications
- Age 18 years or older
- ECOG Performance Status (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death) of 0-2
- Patients must have CT (CAT Scan) measurable disease as defined by RECIST v1.1
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- Willingness and ability to comply with all study procedures
- Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
- Archival tissue available for Foundation One analysis.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
Who cannot join
- Inability to obtain Foundation One testing on archival tissue, or, lack of previous Next Generation Sequencing incorporating testing for NOTCH -1, -2, -3, and -4
- Impaired cardiac function including any one of the following:
- Patients with any of the following laboratory values at baseline: Absolute neutrophil count (ANC) < 1,000/mm3 [SI units 109/L], Platelets < 75,000/mm3 [SI units 109/L], Hemoglobin < 9.0 gm/dL [SI units gm/L], Calculated (e.g. using Cockcroft-Gault formula) or measured creatinine clearance < 50 ml/min, Bilirubin > 1.5 x ULN, except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN, Aspartate transaminase (AST) > 3.0 x ULN, except for patients with liver metastasis who are excluded if AST > 5.0 x ULN, Alanine transaminase (ALT) > 3.0 x ULN, except for patients with liver metastasis who are excluded if ALT > 5.0 x ULN
- Impairment of GI function or GI disease that may significantly alter the absorption of WNT974
- Presence of ≥ CTCAE (Common Terminology Criteria for Adverse Events) Grade 2 toxicity (except alopecia) due to prior therapy
- Malignant disease, other than that being treated in this study. Exceptions to this exclusion criterion include the following: malignancies that were treated curatively, and have not recurred within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancers; and completely resected carcinoma in situ of any type
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- Patients who received anti-cancer therapy prior to the first dose of WNT974 within the following time frames: Biological therapy with a prolonged half-life (e.g., monoclonal antibodies) within 4 weeks, Cytotoxic agents associated with delayed hematologic recovery (e.g., nitrosourea or mitomycin-C) within 6 weeks, Other systemic anti-cancer agents within 3 weeks, Radiotherapy within 2 weeks
- Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with WNT974: Strong inhibitors or inducers of CYP3A4/5, CYP3A4/5 substrates with narrow therapeutic index, known to prolong the QT interval and are also CYP3A4/5 substrates. Refer to Appendix 1 for guidance on concomitant medication.
- Patients who have undergone any major surgery within 2 weeks prior to starting study drug or who have not adequately recovered from previous surgery
- Active hepatitis B or C infection
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 30 days after study treatment. Highly effective contraception methods include: Total abstinence or, male or female sterilization, combination of any two of the following: Use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception. Post-menopausal women are allowed to participate in this study.
- Sexually active males must use a condom during intercourse while taking the drug and for 90 days after stopping treatment and should not father a child in this period.
- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation
- Patients residing in prison.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: An Open Label, Non-randomized Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma
Given that up-regulation of the Wnt pathway has been identified as having a significant role in carcinogenesis in advanced head and neck squamous cell carcinoma, the investigator believes that inhibition of Porcupine via WNT974 will result in tumor control hence improvement in disease free and overall survival in these patients with a tolerable toxicity profile. As suggested by pre-clinical models, patients with a tumor harboring a Notch receptor (any of the four) loss of function mutation may have a greater response rate to treatment with WNT974. The investigator aims to address this question by administration of single agent WNT974 and following response radiologically along with close clinical follow up to monitor toxicities.
- Conditions
- Squamous Cell Carcinoma, Head And Neck
- Being tested
- WNT974
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WNT974Drug
| Study group | Role | What they receive |
|---|---|---|
| WNT974 | Experimental | Patients will receive 10 mg of WNT974 daily by mouth. Receives: Drug: WNT974 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of patients with stable disease, complete response and partial response
Disease control rate will be assessed by examining the number of patients with stable disease, complete and partial response.
Measured: 4 months
Secondary outcomes (4)
Number of patients that respond to treatment
The overall response rate will be determined. Overall response will be defined as the sum of complete response + partial response.
Measured: 4 months
Duration of time from start of treatment to time of progression
Progression free survival in patients with metastatic head and neck cancer will be determined.
Measured: 6 months post treatment
The number of patients alive at 6 months post treatment
Overall survival will be examined.
Measured: 6 months post treatment
The number of patients that experience adverse events
Toxicities associated with the treatment of WNT974 will be assessed.
Measured: 4 weeks post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Primary completionJul 2018 (estimated)
Why it stopped: funding withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma, Head And NeckStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francis Worden, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02649530
- Sponsor's protocol ID
- UMCC 2015.157
- Other IDs
- HUM00108169
- Status last verified
- Sep 2016
- First submitted
- 5 Jan 2016
- Last updated
- 30 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Non-randomized Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02649530
- Acronym / sponsor ID
- UMCC 2015.157
- Conditions
- Squamous Cell Carcinoma, Head And Neck
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: funding withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Primary completion
- Jul 2018 (estimated)
- First posted
- 7 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Given that up-regulation of the Wnt pathway has been identified as having a significant role in carcinogenesis in advanced head and neck squamous cell carcinoma, the investigator believes that inhibition of Porcupine via WNT974 will result in tumor control hence improvement in disease free and overall survival in these patients with a tolerable toxicity profile. As suggested by pre-clinical models, patients with a tumor harboring a Notch receptor (any of the four) loss of function mutation may have a greater response rate to treatment with WNT974. The investigator aims to address this question by administration of single agent WNT974 and following response radiologically along with close clinical follow up to monitor toxicities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| WNT974 | Experimental | Drug: WNT974Patients will receive 10 mg of WNT974 daily by mouth. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically documented diagnosis of locally advanced or metastatic SCC (Squamous Cell Carcinoma) of the head and neck no longer amenable to curative surgical resection or radiation therapy.
- Refractory to platinum-based therapy (defined as disease progression within 6 months of last dose of platinum chemotherapy)
- Patient is able swallow and absorb oral medications
- Age 18 years or older
- ECOG Performance Status (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death) of 0-2
Key exclusion criteria (15 listed)
- Inability to obtain Foundation One testing on archival tissue, or, lack of previous Next Generation Sequencing incorporating testing for NOTCH -1, -2, -3, and -4
- Impaired cardiac function including any one of the following:
- Patients with any of the following laboratory values at baseline: Absolute neutrophil count (ANC) < 1,000/mm3 [SI units 109/L], Platelets < 75,000/mm3 [SI units 109/L], Hemoglobin < 9.0 gm/dL [SI units gm/L], Calculated (e.g. using Cockcroft-Gault formula) or measured creatinine clearance < 50 ml/min, Bilirubin > 1.5 x ULN, except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN, Aspartate transaminase (AST) > 3.0 x ULN, except for patients with liver metastasis who are excluded if AST > 5.0 x ULN, Alanine transaminase (ALT) > 3.0 x ULN, except for patients with liver metastasis who are excluded if ALT > 5.0 x ULN
- Impairment of GI function or GI disease that may significantly alter the absorption of WNT974
- Presence of ≥ CTCAE (Common Terminology Criteria for Adverse Events) Grade 2 toxicity (except alopecia) due to prior therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WNT974 | Drug | WNT974 |
Primary outcome
The number of patients with stable disease, complete response and partial response
Time frame: 4 months
Disease control rate will be assessed by examining the number of patients with stable disease, complete and partial response.
4 secondary outcomes
Number of patients that respond to treatment
Time frame: 4 months
Duration of time from start of treatment to time of progression
Time frame: 6 months post treatment
The number of patients alive at 6 months post treatment
Time frame: 6 months post treatment
The number of patients that experience adverse events
Time frame: 4 weeks post treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francis Worden, M.D. principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing WNT974 in people with Squamous Cell Carcinoma, Head And Neck, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of patients with stable disease, complete response and partial response (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2016.